How Does DNA Work?

How Does DNA Work?

DNA, Chromosomes, and Genes

DNA is the chemical that carries our genetic information, with our entire genome (complete DNA set) residing in almost every body cell. We can describe DNA at different scales; most commonly chromosomes and genes.

The difference between genes, chromosomes, DNA, and the genome is illustrated by the analogy of a recipe book

If the human genome is a recipe book, then chromosomes are the chapters, and genes the recipes. They're all made of deoxyribonucleic acid (DNA).

Stored permanently in the nucleus, DNA coils up into chromosomes to prevent it from tangling or becoming damaged when a cell divides.

How genes coil into chromosomes

How genes coil into chromosomes.

Meanwhile, genes are the long sequences of nucleic acid bases—namely adenine (A), cytosine (C), thymine (T), and guanine (G)—that match up in pairs to form the rungs on the DNA ladder.

When not condensed into chromosomes, DNA is only just visible under a light microscope, seen as fine strands known as chromatin. It was in 1953 that Watson and Crick famously intuited the double helix shape of DNA chromatin.

They already suspected that DNA was make of two spines winding around each other, thanks to Franklin's x-ray crystallography of DNA. And Chargaff, who analysed ratios of DNA bases in different organisms, gave them the crucial tip-off that adenine matches with thymine, while guanine matches with cytosine.

This is how Watson and Crick ended up using cardboard cutouts at their desk to model the most iconic of molecules. They managed to resolve the molecular jigsaw puzzle by linking the four bases together like the rungs on a ladder, while ribose sugars and phosphate groups formed the rails.

Illustration of the structure of DNA: bases (A, C, G, T) form the rungs while a sugar-phosphate backbone forms the rails of a winding ladder

The structure of DNA is rulebound and repetitive—it's the precise sequence of bases that creates genetic diversity. The Mysterious World of The Human Genome by Frank Ryan gives the analogy of a train track that stretches out to the horizon, with three billion sleepers representing base pairs.

The base pairing system is pretty reliable, but mistakes do occur during replication, creating genetic mutations. In such cases, rare bonds can form between non-matching bases to lock them in place.

DNA replication errors are caused by mispairings, such as when normal bases form bonds between different atoms (eg, allowing thymine to pair with guanine), or when bases gain an extra proton (eg, allowing adenine to pair with cytosine). The resulting mutation can change the function of the gene, sometimes manifesting in disease.

DNA replication errors are caused by mispairings, such as when normal bases form bonds between different atoms (eg, allowing thymine to pair with guanine), or when bases gain an extra proton (eg, allowing adenine to pair with cytosine). The resulting mutation can change the function of the gene, sometimes manifesting in disease.

How Does DNA Work?

Now we have the structure, how does DNA work? How does it physically produce our bodies? If DNA is the recipe book, who's putting together the ingredients and what do they make?

Let's briefly consider the overall structure of cells: the multipurpose biological factories that make up our tissues. Cells have complex internal structures bustling with organelles and proteins that keep us alive.

Animal Cell Diagram Cartoon Style

The basic features of an animal cell. DNA is stored in the nucleus like a reference library, informing the production of all cell components as well as the molecules secretes beyond.

Proteins are large, complex molecules that provide structure, catalyse reactions, transport molecules, and send chemical signals. Whether they're retained within the cell or secreted elsewhere, they do much of the work in the body. Hormones, antibodies, and enzymes all types of proteins.

DNA isn't just a blueprint for foetal growth; it's essential for day-to-day survival, such as making insulin if we've just had breakfast, or cortisol to regulate our stress response.

So how does DNA work? Crick's Central Dogma is a three-step process of transcription, RNA processing, and translation. This is how genetic information is converted into all the molecules that make us.

The Central Dogma of DNA expression explains how DNA works using transcription, RNA processing, and translation

The Central Dogma of DNA expression describes the one-way flow of genetic information from DNA to proteins using transcription, RNA processing, and translation.

Step 1. Transcription

Transcription is the process of copying double-stranded DNA into single-stranded RNA.

In the cell nucleus, an enzyme known as RNA polymerase travels along the DNA helix. The two strands are teased apart and unwound to expose the anti-sense strand. This template is used to string free-floating nucleotides together to create a copy as RNA.

DNA Transcription Illustration

The process of DNA transcription. (1) Initiation sees an enzyme called RNA polymerase bind to a promoter sequence located at the start of a gene. (2) The double helix is unwound to expose the anti-sense template strand. (3) Elongation sees RNA polymerase read the template one nucleotide at a time and construct a pre-mRNA transcript from free-floating nucleotides. (4) Once translated, the two strands of DNA are rewound back into a double helix. (5) The pre-mRNA strand grows in length until the RNA polymerase reaches a terminator sequence, signalling the end of transcription.

In the process of transcribing DNA into RNA, the nucleotide thymine (T) is switched out for a very similar molecule called uracil (U). This is one of the notable differences between DNA and RNA as molecules.

Why convert it to RNA at all? For one, it keeps the master DNA recipe away from the busy kitchen floor in case the cooks accidentally spill bolognaise sauce on it.

Step 2. RNA Processing

RNA processing edits down the genetic sequence, as well as adding a cap and tail to prevent degradation.

Here's another reason to use RNA: the DNA recipe book is written in such a way that different paragraphs can be cut-and-paste to create whole new viable recipes. We definitely don't want these edits being made to our master copy, so we edit disposable copies instead.

In alternative splicing, non-coding sequences of RNA called introns are excised, leaving behind only coding sequences called exons. This adds remarkable versatility: by selecting which exons to use, the same genetic sequence can produce multiple different protein products.

Finally, a cap and tail are added to the start and end of the sequence to prevent the ends from degrading.

RNA Processing Illustration

During RNA processing, enzymes called spliceosomes remove non-coding introns, leaving behind only coding exons to vary the end product. A 5' cap is added to the start of the sequence and a 3' tail is added to the end.

Step 3. Translation

Translation converts the mRNA into long chains of amino acids, which fold to make functional proteins.

Now the mRNA recipe is ready for the kitchen floor. It exits the nucleus and lands in the cell cytoplasm for translation. This stage is named for the fact that it involves a change of language, from bases to amino acids.

A molecular complex called a ribosome binds to the mRNA cap and moves along its length, reading the bases in groups of three (codons). Free-floating transfer RNA (tRNA) units with complimentary anticodons bring amino acids to the ribosome.

DNA Translation Illustration

The process of DNA translation. (1) Free-floating tRNAs bring amino acids in for translation. (2) The ribosome holds the mRNA in place while matching tRNAs bind to codons. (3) The amino acid is linked to the growing polypeptide chain and the mRNA is shifted to the next codon. (4) The tRNA moves away having deposited its amino acid. Termination occurs when the ribosome reaches a stop codon and releases the polypeptide chain.

This repetitive matching process gives rise to chains of 50-2,000 amino acids called polypeptides, which fold into functional proteins. In its linear form, the polypeptide has a primary structure. Further bonding between the amino acids can create alpha-helices and beta-pleated sheets, described as the secondary structure.

When folding creates complex 3D shapes, the protein is described as having a tertiary structure. And when two or more polypeptides join together, it gives rise to a quaternary structure. Haemoglobin (the protein that carries oxygen in red blood cells) is one example of a protein with quaternary structure.

The Genetic Code

"Tell me more about the codons!" I hear you scream. And you'd be right. This is a good thing to scream about, if anything is.

The genetic code describes the relationship between codons and amino acids. There are 64 possible codons (4 x 4 x 4), yet only 20 amino acids produced by the human body (out of some 500 amino acids in nature). This means most amino acids in humans are specified by more than one codon.

The codon table lays it all out for us. At the start of an mRNA sequence, the codon AUG performs as a start signal as well as the amino acid methionine. At the end of the mRNA strand, three possible codons (UAG, UGA, and UAA) perform as stop signals.

The genetic code describes how each three-letter codon translates to specific amino acids

The genetic code describes how each three-letter codon translates to specific amino acids.

Ala = Alanine Leu = Leucine
Arg = Arginine Lys = Lysine
Asn = Asparagine Met = Methionine
Asp = Aspartic Acid Phe = Phenylalanine
Cys = Cysteine Pro = Proline
Gln = Glutamine Ser = Serine
Glu = Glutamic Acid Thr = Threonine
Gly = Glycine Trp = Tryptophane
His = Histidine Tyr = Tyrosine
Ile = Isoleucine Val = Valine

Having multiple codons translate to the same amino acid actually dampens the effects of mutations that could cause disease. For instance, a point mutation from GUU to GUC still produces the amino acid valine, so an error in a single nucleotide is less likely to disrupt the functional shape of a protein.

Here's a summary of how DNA works to produce those amino acid chains and proteins.

The Central Dogma summary: DNA to RNA to amino acids to proteins

The Central Dogma in summary.

How fast does DNA work in the human body? At scale, our genes are translated at an astonishing rate. A single ribosome can produce dozens of polypeptide chains every second. And there are 10 million ribosomes at work in a typical cell, throwing off proteins alongside all its sister cells.

It's all rather amazing really. DNA and its entourage of enzymes perform a constant choreography, culminating in the normal functioning of any living organism, such as a friendly newt or toad. Isn't that brilliant?

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